The major objective of this work is to determine the nature and origin of the human atypical lymphocyte. The study focuses on atypical cells in the context of Epstein-Barr virus (EBV) induced infectious monoucleosis (IM). It seeks to determine the mechanisms of generation of the cells, their characteristics, their role in disease and their relevance to control of potentially malignant lymphoproliferation. An in vitro model has been established in which peripheral leukocytes from EBV seropositive and seronegative donors are stimulated with inactivated virus. Cytotoxic blast cells, which resemble the atypical cells of IM are generated. Kinetic studies reveal that up to 10 percent of the total lymphocyte population is activated and the the response is polyclonal. We are now principally concerned with how and why such a vigorous response is generated. We are examining the possibility that since there is a receptor for EBV (EBVR) on the B cell, it may in part be induced by antigen presented by the B cell. EBV-receptor-like activity has been isolated from B cell lines and used to prepare an antibody with anti-receptor-like activity. This antiserum will be further characterized and used for depletion and isolation of EBVR cells. This will allow us to study the effects of EBV on isolated EBVR+ cells and determine the effects of EBV/B cell complexes on the EBVR+ depleted population. The ultimate objectives of the proposal are to determine whether the atypical cell is a common link between IM induced by various agents, why it is particularly prone to induction of EBV and whether this may have general implication for the control of proliferative disease.